Abel was born in 1969 in Chicago, Illinois, and raised in the Chicago metropolitan area. She graduated from Evanston Township High School. She attended Carleton College for in 1987-88, and then transferred to the University of Chicago, where she published her first comics work in 1988, in the student anthology Breakdown. She graduated with a BA degree. Additionally, she worked for three years in the administration at the School of the Art Institute of Chicago.

Abel started self-publishing the photocopied, hand-sewn and embellished' comic book Artbabe in 1992; four annual issues followed, with Abel having won a Xeric Foundation grant to self-publish and distribute issue #5. This was the first professionally printed Artbabe, and was subtitled "The Four Seasons". With the publication of the Xeric issue of Artbabe, Abel came to the attention of Fantagraphics publisher Gary Groth, who offered to publish the series. Each issue of Artbabe contained one or more complete stories; Abel did not begin any longer sequential work until La Perdida in 2000. The character Artbabe, who appears on every cover, does not actually appear in any of the stories.

In 1998, Abel moved to Mexico City with her boyfriend, now husband, comics artist Matt Madden. She went on hiatus from Artbabe in 1999. From 1996-2005, Abel did a series of one-page journalistic comics for the University of Chicago Magazine, and also embarked on Radio: an Illustrated Guide for the radio program "This American Life". This book depicted how an episode of the show is made, with behind-the-scenes reportage and a how-to guide to creating a radio show at home.

After two years in Mexico City, Abel moved to Brooklyn, New York. Abel created the five-issue, 250-page series La Perdida. Published by Fantagraphics Books, it concerns a Mexican-American woman, Carla, raised by her Anglo mother, who moves on a whim to Mexico City to search for her identity. It was first published by Fantagraphics Books between 2000 and 2005 as a five-part mini-series. Abel revised the text for its compilation and publication in 2006 as a hardcover volume by Pantheon Books. The book has received a positive critical response.

Abel teaches undergraduate cartooning courses at the School of Visual Arts, and gives workshops at other locations, such as Ox-Bow Summer School of Art. She appeared as a character in the back-cover story of Hate #10 by Peter Bagge. She has stated that her major work is not autobiographical, and that although she is a feminist, her work is not explicitly political.

In 2008, Abel and Madden produced Drawing Words and Writing Pictures for First Second. The book is a product of the years Abel and Madden have spent as teachers, is a comprehensive manual on creating comics. That same year, Abel also collaborated on Life Sucks, written with Gabe Soria and Warren Pleece.

Abel's one-person exhibitions include "Corridoio Altervox" in Rome, the Phoenix Gallery in Brighton; the Oporto International Comics Festival in Portugal, Viñetas desde o Atlántico in A Coruna, Spain, and the Naples Comicon.
Her group exhibitions include the Jean Albano Gallery in Chicago, Athaneum, Stripdagen, in the Netherlands, the Davidson Galleries in Seattle, the Forbes Gallery at the Hyde Park Art Center, in New York, the Regina Miller Gallery and Vox Gallery in Philadelphia, Centre National de la Bande Dessinée et de l'Image in Angoulême, France, and the Norman Rockwell Museum in Stockbridge, Massachusetts.

In addition to the Xeric Grant, she has also won the Harvey and Lulu Award for Best New Talent (both in 1997), the Harvey Award for Best New Series (for La Perdida) and the Chicago Artists International Program Grant